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Submitted on July 29, 2005
Accepted on October 17, 2005
Dept. of Reproductive Biology, and Dept. of Medicine, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44109
* To whom correspondence should be addressed. E-mail: fgonzalez{at}metrohealth.org.
Context: Insulin resistance and chronic low level inflammation are often present in women with Polycystic Ovary Syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNC) in PCOS. Design: A prospective controlled study. Setting: An academic medical center. Patients: Sixteen women with PCOS (8 lean, 8 obese) and 15 age- and body composition-matched controls (8 lean, 7 obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-hour 75 gram oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P < 0.003). The % change in ROS generation from MNC was higher in lean and obese PCOS compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P < 0.003). The % change in ROS generation from MNC correlated positively with glucose area under the curve (r=0.38, P < 0.05), and plasma levels of testosterone (r=0.59, P < 0.002) and androstenedione (r=0.50, P < 0.009). The % change in p47phox from MNC was also higher in lean and obese PCOS compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. -13.7 ± 8.7, P < 0.02), and correlated negatively with ISOGTT (r= -0.39, P < 0.05). Conclusion: ROS generation from MNC in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.
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